Id2 and Id4 are not the major negative regulators of oligodendrocyte differentiation during early central nervous system development
Id2 and Id4 are not the major negative regulators of oligodendrocyte differentiation during early central nervous system development
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Id2 和 Id4 不是早期中枢神经系统发育过程中少突胶质细胞分化的主要负调节因子。
DOI：
10.1002/glia.24126
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发表时间：
2021-12-10
期刊：
影响因子：
6.2
通讯作者：
Qiu, Mengsheng
中科院分区：
文献类型：
--
作者：
Huang, Hao;Wu, Huihui;Qiu, Mengsheng
髓鞘保证神经冲动的快速传导，为神经元提供营养支持。髓鞘由中枢神经系统中分化的少突胶质细胞（OL）形成。在OL发育过程中，少突胶质祖细胞（OPCs）向成熟OL的分化受到正分化因子（驱动因子）和负调节因子（制动因子）的双重控制。以前的研究表明，Id 2和Id 4是OL分化的关键负性因素。然而，这些结论主要基于体外研究，并且Id 4突变体中报告的OL表型似乎是轻微的。在这项研究中，我们系统地研究了Id 2和Id 4基因在OL分化的遗传突变体和胚胎鸡脊髓中的体内功能。我们的研究结果表明，Id 4的破坏对OL分化和成熟没有影响，而Id 2突变体和Id 2/Id 4复合突变体显示出轻度和短暂的OL分化早熟。与这些功能丧失研究一致，Id 2而不是Id 4在OPCs中弱表达。尽管它们在OL分化中的作用较小，但在胚胎鸡脊髓中强制表达Id 2和Id 4强烈抑制OPCs的分化。两者合计，我们详细的功能和表达的研究强烈表明，Id 2和Id 4不是在动物发育过程中的OPC分化的主要体内阻遏物，脱落的早期OL发展的分子调控新的光。
Myelin sheathes ensure the rapid conduction of neural impulse and provide nutritional support for neurons. Myelin sheathes are formed by differentiated oligodendrocytes (OLs) in the central nervous system. During OL development, the differentiation of oligodendrocyte progenitor cells (OPCs) into mature OLs is controlled by both positive differentiation factors (drivers) and negative regulatory factors (brakes). Previous studies have suggested Id2 and Id4 as the key negative factors for OL differentiation. However, these conclusions were mainly based on in vitro studies and the reported OL phenotype in Id4 mutants appear to be mild. In this study, we systematically investigated the in vivo function of Id2 and Id4 genes in OL differentiation in their genetic mutants and in embryonic chicken spinal cord. Our results showed that disruption of Id4 has no effect on OL differentiation and maturation, whereas Id2 mutants and Id2/Id4 compound mutants display a mild and transient precocity of OL differentiation. In agreement with these loss-of-function studies, Id2, but not Id4, is weakly expressed in OPCs. Despite their minor roles in OL differentiation, forced expression of Id2 and Id4 in embryonic chicken spinal cords strongly inhibit the differentiation of OPCs. Taken together, our detailed functional and expressional studies strongly suggest that Id2 and Id4 are not the major in vivo repressors of OPC differentiation during animal development, shedding new light on the molecular regulation of early OL development.